It is well known that cytokines play an important role in oral diseases. Furthermore, increased levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) have been reported in patients with cancer and premalignant lesions such as oral lichen planus and oral submucous fibrosis. The aim of this study was to assess salivary IL-6 and TNF-alpha levels in 30 patients with histopathologically confirmed leukoplakia (age range 24-78, mean 52.3 years) in comparison to 34 controls (age range 27-79, mean 52 years). Salivary IL-6 and TNF-alpha were determined by enzyme linked immunoadsorbent assay. Statistical analysis was performed by use of Mann-Whitney test for independent samples and values lower than 0.05 were considered as significant (p<0.05). Significantly higher levels of salivary IL-6 and TNF-alpha in patients with oral leukoplakia when compared to healthy controls were found. The levels of salivary IL-6 and TNF-alpha did not correlate with the size of leukoplakia (lesions) nor with its localization regarding high and low risk sites for malignant transformation. Levels of salivary IL-6 and TNF-alpha were not influenced by smoking habits. We can conclude that increased salivary IL-6 and TNF-alpha might play a certain role in oral leukoplakia.